Lutein suppresses hyperglycemia-induced premature senescence of retinal pigment epithelial cells by upregulating SIRT1

Hyperglycemia contributes to the pathogenesis of diabetic complications, such as diabetic retinopathy, by affecting cellular redox state. In this study, we investigated the effects of lutein on hyperglycemia-induced premature senescence in retinal pigment epithelium (RPE) cells. In ARPE-19 cells, a spontaneously immortalized cell line derived from human RPE, lutein treatment significantly inhibited high glucose-triggered premature senescence and production of reactive oxygen species (ROS). Notably, lutein treatment increased SIRT1 mRNA and protein levels, suggesting that lutein exerted its beneficial effects in these cells by upregulating SIRT1 expression. Resveratrol, an activator of SIRT1, mimicked the inhibitory effects of lutein on high glucose-induced premature senescence and ROS generation, whereas sirtinol, a specific inhibitor of SIRT1, blocked these effects of lutein. Collectively, these observations indicate that lutein interferes with hyperglycemia-induced RPE senescence by modulating SIRT1 signaling.